The TGF-β signaling pathway involves several genes, and pathogenic variants in some of these genes have been shown to be associated with the development of orofacial clefts, such as the variants in the Interferon Regulatory Factor 6 (IRF6) gene associated with Van der Woude syndrome (VWS) [3]; the SMAD gene family, which also cross-interacts with the BMP signaling pathway; and variants in these genes are associated with an increased risk of cleft lip development [18]. Here, IRF6 is linked to van der Woude syndrome.